This project is aimed in part at developing compounds that can bind to peptides and proteins in water solution with specific recognition of their structures. Compounds are being made that are comprised of two or three cage components, each of which can bind an amino acid sidechain, along with other units to interact with charged groups. Selective binders could be direct leads into novel medicinal compounds, since they would block the binding of hormones to receptors, or of proteins to each other. Such binding could have useful biological effects in many disease: the binding of peptides to their receptors-or of proteins to each other in dimmers or aggregates-are important aspects of many biological processes, including undesirable ones. The second part of the project deals with the invention and study of novel catalysts that imitate enzymes. It furnishes the simple chemistry relevant to understanding biological chemistry, and such understanding is frequently used as a guide in the development of new medicinals. Also, the chemistry performed in Nature is more effective and more selective than has yet been achieved with related non- biological chemistry. The development of selective chemistry that imitates biological chemistry could be of great use in chemical synthesis, including the synthesis of medicinals. Enzymes typically catalyze reactions by binding their substrates, using hydrophobic and other forces, and then catalyzing the specific needed reaction with two or more catalytic groups, either from the protein sidechains or from coenzymes. In this project the binding will be done with readily available cyclodextrins, or with other synthetic cavity molecules, while the catalysis will be done with acid/base groups, with coenzyme groups, or with metal ions. It is expected that good catalysts can be produced by adjusting the geometric relationships in the catalyst/substrate complexes, and that this will help us understand the reason for rapid catalysis by enzymes. It will also help us design useful catalysts. They may prove to be useful medicinals in their own right, replacing or augementing catalysis by natural enzymes. For this to be possible, it is important that they function in water solution, as they are designed to do.